Diallyl Trisulfide Augments Ischemia-Induced Angiogenesis via an Endothelial Nitric Oxide Synthase-Dependent Mechanism
| Autor: | Kazuhisa Kondo, John W. Calvert, Sumio Morita, Rei Shibata, Kazumasa Unno, Toyoaki Murohara, Yuuki Shimizu, Ryo Hayashida, Satoshi Shintani |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Endothelium Nitric Oxide Synthase Type III Angiogenesis Allyl compound Neovascularization Physiologic Apoptosis 030204 cardiovascular system & hematology Pharmacology Sulfides medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Enos Ischemia mental disorders medicine Animals Protein kinase B Mice Knockout biology Endothelial Cells General Medicine biology.organism_classification Hindlimb Endothelial stem cell Allyl Compounds Oxidative Stress 030104 developmental biology Diallyl trisulfide medicine.anatomical_structure chemistry Cardiology and Cardiovascular Medicine Proto-Oncogene Proteins c-akt Oxidative stress Blood Flow Velocity Signal Transduction |
| Zdroj: | Circulation journal : official journal of the Japanese Circulation Society. 81(6) |
| ISSN: | 1347-4820 |
| Popis: | Background Hydrogen sulfide (H2S) exerts beneficial actions against the development of cardiovascular disease. Diallyl trisulfide (DATS) is an organic polysulfide found in garlic oil that liberates H2S under physiological conditions. This study investigated whether DATS modulates endothelial cell function, as well as revascularization processes in a mouse model of hind-limb ischemia.Methods and Results:Wild-type (WT), endothelial nitric oxide synthase-deficient (eNOS-KO) and Akt1-heterogenic deficient (Akt-Het) mice were subjected to unilateral hindlimb ischemia (HLI). DATS or a vehicle control was injected into the abdomen of mice for up to 10 days following HLI induction. Treatment with DATS enhanced blood flow recovery and capillary density in the ischemic limbs of WT mice. This was accompanied by a reduction in apoptotic activity and oxidative stress in the ischemic muscles. DATS also increased the phosphorylation of Akt and eNOS in ischemic muscles. In contrast to WT mice, DATS did not improve blood flow of eNOS-KO and Akt-Het mice. In cultured human umbilical vein endothelium cells, DATS decreased apoptotic activity and oxidative stress under hypoxic conditions, and stimulated the phosphorylation of Akt and eNOS. Inhibition of Akt or NOS signaling reversed DATS-stimulated eNOS phosphorylation and blocked the effects of DATS on apoptosis and oxidative stress. Conclusions These observations suggest that DATS promotes revascularization in response to HLI through its ability to stimulate the Akt-eNOS signaling pathway. |
| Databáze: | OpenAIRE |
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